Tensin 1 regulated by hepatic leukemia factor represses the progression of prostate cancer.

Abstract

Hepatic leukemia factor (HLF), a transcription factor, is dysregulated in many cancers. This study investigates the function of HLF in prostate cancer (PCa) and its relation to tensin 1 (TNS1). Clinical tissues were collected from 24 PCa patients. Duke University 145 (DU145) and PC3 cells overexpressing HLF were established. HLF signaling was downregulated in PCa tissues compared to adjacent tissues and in DU145 and PC3 cells compared to prostate epithelial cells RWPE-1 or prostate stromal cells (WPMY-1). PCa cell lines with overexpression of HLF had reduced proliferative, migratory, and invasive activity, increased apoptosis, and cell mitosis mostly in the G0/G1 phase. HLF induced the TNS1 transcription to activate the p53 pathway. Depletion of TNS1 reversed the anti-tumor effects of HLF on PCa cells and tumor growth and metastasis in vivo. In summary, our findings suggest that HLF suppressed PCa progression by upregulating TNS1 expression and inducing the p53 pathway activation, which might provide insights into novel strategies for combating PCa.